Will blood-informed design signal the fourth generation of cardiac assist devices?

Mechanical circulatory support devices have profoundly transformed the management of severe cardiothoracic disorders. While heart transplantation is the gold standard therapy for end-stage heart disease, long-term mechanical support devices are a viable alternative for those ineligible and/or those awaiting organ availability. Major technological advancements were made over first 5 decades of development, resulting in improved durability and survival with reduced adverse events. However, gains have tapered recently for various complications (e.g., internal bleeding, multisystem organ failure), which collectively represent a significant proportion of disability and/or mortality. Further, in light of mature ventricular assist devices failing during clinical trials or even after clinical approval (class I withdrawals), it is timely to consider: Are our preclinical assessment protocols vital in the design and development of mechanical circulatory support devices, providing a realistic and reliable profile of future clinical performance? This commentary explores this question and analyses development pathways through the lens of the various disciplines involved in the preclinical assessment of mechanical circulatory support technologies: Limitations in approaches to benchtop blood testing, computational design and simulation, and animal testing are discussed as likely contributors to some of the common hemocompatibility-related adverse events (HRAEs). While it is acknowledged that some shortcomings are pragmatic in nature, possible solutions are presented that will only be realized through truly transdisciplinary and open approaches that challenge the current nature of medical device development. We suggest that these can and must be overcome to diminish HRAEs and will potentially demarcate the fourth generation of cardiac assist devices.

Left ventricular unloading via percutaneous assist device during extracorporeal membrane oxygenation in acute myocardial infarction and cardiac arrest.

INTRODUCTION: A feared complication of an acute myocardial infarction (AMI) is cardiac arrest (CA). Even if return of spontaneous circulation is achieved, cardiogenic shock (CS) is common. Venoarterial extracorporeal membrane oxygenation (VA-ECMO) supports patients with CS and is often used in conjunction with an Impella device (2.5 and CP) to off-load the left ventricle, although limited evidence supports this approach. METHODS: The goal of this study was to determine whether a mortality difference was observed in VA-ECMO alone versus VA-ECMO with Impella (ECPELLA) in patients with CS from AMI and CA. A retrospective chart review of 50 patients with AMI-CS and CA and were supported with VA-ECMO (n = 34) or ECPELLA (n = 16) was performed. The primary outcome was all-cause mortality at 6-months from VA-ECMO or Impella implantation. Secondary outcomes included in-hospital mortality and complication rates between both cohorts and intensive care unit data. RESULTS: Baseline characteristics were similar, except patients with ST-elevation myocardial infarction were more likely to be in the VA-ECMO group (p = 0.044). The ECPELLA cohort had significantly worse survival after VA-ECMO (SAVE) score (p = 0.032). Six-month all-cause mortality was not significantly different between the cohorts, even when adjusting for SAVE score. Secondary outcomes were notable for an increased rate of minor complications without an increased rate of major complications in the ECPELLA group. CONCLUSIONS: Randomized trials are needed to determine if a mortality difference exists between VA-ECMO and ECPELLA platforms in patients with AMI complicated by CA and CS.

Percutaneous Venopulmonary Extracorporeal Membrane Oxygenation as Bridge to Lung Transplantation.

Mechanical circulatory support (MCS) as a bridge to lung transplant is an infrequent but accepted pathway in patients who have refractory end-stage pulmonary failure. The American Association of Thoracic Surgeons Expert Consensus Guidelines, published in 2023, recommends venovenous (VV) extracorporeal membrane oxygenation (ECMO) as the initial configuration for those patients who have failed conventional medical therapy, including mechanical ventilation, while waiting for lung transplantation and needing MCS. Alternatively, venoarterial (VA) ECMO can be used in patients with acute right ventricular failure, hemodynamic instability, or refractory respiratory failure. With the advancement in percutaneous venopulmonary (VP) ECMO cannulation techniques, this option is becoming an attractive configuration as bridge to lung transplantation. This configuration enhances stability of the right ventricle, prevents recirculation with direct introduction of pulmonary artery oxygenation, and promotes hemodynamic stability during mobility, rehabilitation, and sedation-weaning trials before lung transplantation. Here, we present a case series of eight percutaneous VP ECMO as bridge to lung transplant with all patients mobilized, awake, and successfully transplanted with survival to hospital discharge.

Extracorporeal Carbon Dioxide Removal to De-escalate Venovenous Extracorporeal Membrane Oxygenation in Severe COVID-19 Acute Respiratory Distress Syndrome.

OBJECTIVES: In a subset of patients with COVID-19 acute respiratory distress syndrome (ARDS), there is a need for extracorporeal membrane oxygenation (ECMO) for pulmonary support. The primary extracorporeal support tool for severe COVID-19 ARDS is venovenous (VV) ECMO; however, after hypoxemic respiratory failure resolves, many patients experience refractory residual hypercarbic respiratory failure. Extracorporeal carbon dioxide removal (ECCO2R) for isolated hypercarbic type II respiratory failure can be used in select cases to deescalate patients from VV ECMO while the lung recovers the ability to exchange CO2. The objective of this study was to describe the authors' experience in using ECCO2R as a bridge from VV ECMO. DESIGN: Hemolung Respiratory Assist System (RAS) is a commercially available (ECCO2R) device, and the United States Food and Drug Administration accelerated its use under its Emergency Use Authorization for the treatment of refractory hypercarbic respiratory failure in COVID-19-induced ARDS. This created an environment in which selected and targeted mechanical circulatory support therapy for refractory hypercarbic respiratory failure could be addressed. This retrospective study describes the application of Hemolung RAS as a VV ECMO deescalation platform to treat refractory hypercarbic respiratory failure after the resolution of hypoxemic COVID-19 ARDS. SETTING: A quaternary-care academic medical center, single institution. PARTICIPANTS: Patients with refractory hypercarbic respiratory failure after COVID-19 ARDS who were previously supported with VV ECMO. MEASUREMENTS AND MAIN RESULTS: Twenty-one patients were placed on ECCO2R after VV ECMO for COVID-19 ARDS. Seventeen patients successfully were transitioned to ECCO2R and then decannulated; 3 patients required reescalation to VV ECMO secondary to hypercapnic respiratory failure, and 1 patient died while on ECCO2R. Five (23.8%) of the 21 patients were transitioned off of VV ECMO to ECCO2R, with a compliance of <20 (mL/cmH2O). Of these patients, 3 with low compliance were reescalated to VV ECMO. CONCLUSIONS: Extracorporeal carbon dioxide removal can be used to continue supportive methods for patients with refractory type 2 hypercarbic respiratory failure after COVID-19 ARDS for patients previously on VV ECMO. Patients with low compliance have a higher rate of reescalation to VV ECMO.

Technical considerations for percutaneous pulmonary artery cannulation for mechanical circulatory support.

Objectives: Percutaneous pulmonary artery cannulas, used as inflow for left ventricular venting or as outflow for right ventricular mechanical circulatory support, are easily and rapidly deployable with transesophageal and fluoroscopic guidance. Methods: We chose to review our institutional and technical experience with all right atrium to pulmonary artery cannulations. Results: Based on the review, we describe 6 right atrium to pulmonary artery cannulation strategies. They are divided into total right ventricular assist support, partial right ventricular assist support, and left ventricular venting. A single limb cannula or a dual lumen cannula can be used for right ventricular support. Conclusions: In the right ventricular assist device configuration, percutaneous cannulation may prove beneficial in cases of isolated right ventricular failure. Conversely, pulmonary artery cannulation can be used for left ventricular venting as drainage to a cardiopulmonary bypass or extracorporeal membrane oxygenation circuit. This article can be used as a reference for the technical aspects of cannulation, decision-making in patient selection, and management of patients in these clinical scenarios.

Oxygenated right ventricular assist device as part of veno-venopulmonary extracorporeal membrane oxygenation to support the right ventricle and pulmonary vasculature.

COVID-19 infection can lead to severe acute respiratory distress syndrome (ARDS), right ventricular (RV) failure and pulmonary hypertension. Venovenous extracorporeal membrane oxygenation (V-V ECMO) has been used for patients with refractory hypoxemia. More recently dual-lumen right atrium to pulmonary artery oxygenated right ventricular assist devices (Oxy-RVAD) have been utilized in the severe medical refractory COVID ARDS setting. Historically, animal data has demonstrated that high continuous non-pulsatile RVAD flows, leading to unregulated and unprotected circulation through the pulmonary vessels is associated with an increased risk of pulmonary hemorrhage and increased amount of extravascular lung water. These risks are heightened in the setting of ARDS with fragile capillaries, left ventricular (LV) diastolic failure, COVID cardiomyopathy, and anticoagulation. Concurrently, due to infection, tachycardia, and refractory hypoxemia, high V-V ECMO flows to match high cardiac output are often necessary to maintain systemic oxygenation. Increase in cardiac output without a concurrent increase in VV ECMO flow will result in a higher fraction of deoxygenated blood returning to the right heart and therefore resulting in hypoxemia. Several groups have suggested using a RVAD only strategy in COVID ARDS; however, this exposes the patients to the risk of pulmonary hemorrhage. We present one of the first known cases using an RV mechanical support, partial flow pulmonary circulation, oxygenated Veno-venopulmonary (V-VP) strategy resulting in RV recovery, total renal recovery, awake rehabilitation, and recovery.

Intracannula Thrombus Formation Associated With Dual Lumen ProtekDuo Cannula in Extracorporeal Membrane Oxygenation (ECMO).

Extracorporeal membrane oxygenation (ECMO) is used in cases of severe respiratory failure refractory to medical management. Use of ECMO is increasing, along with new cannulation strategies including oxygenated right ventricular assist devices (oxy-RVADs). Multiple dual lumen cannulas are now available, which increase the potential for patient mobility and decrease the number of vascular access sites. However, dual lumen, single cannula flow can be limited by adequate inflow, requiring the need for an additional inflow cannula to meet patient demands. This cannula configuration may result in differential flows in the inflow and outflow limbs and altered flow dynamics, increasing the risk of intracannula thrombus. We describe a series of four patients treated with oxy-RVAD for COVID-19-associated respiratory failure complicated by dual lumen ProtekDuo intracannula thrombus.

Subacute groin complications related to ECMO cannulation are associated with longer hospitalizations.

Subacute groin complications associated with extracorporeal membrane oxygenation (ECMO) cannulation are well recognized, yet their effects on clinical outcomes remain unknown. This single-center, retrospective study reviewed all patients receiving venoarterial ECMO from 01/2017 to 02/2020. Cohorts analyzed included transplanted patients (TPs) and non-transplanted patients (N-TPs) who did or did not develop ECMO-related subacute groin complications. Standard descriptive statistics were used for comparisons. Logistic regressions identified associated risk factors. Overall, 82/367 (22.3%) ECMO patients developed subacute groin complications, including 25/82 (30.5%) seromas/lymphoceles, 32/82 (39.0%) hematomas, 18/82 (22.0%) infections, and 7/82 (8.5%) non-specified collections. Of these, 20/82 (24.4%) underwent surgical interventions, most of which were muscle flaps (14/20, 70.0%). TPs had a higher incidence of subacute groin complications than N-TPs (14/28, 50.0% vs. 68/339, 20.1%, P = 0.001). Seromas/lymphoceles more often developed in TPs than N-TPs (10/14, 71.4% vs. 15/68, 22.1%, P = 0.001). Most patients with subacute groin complications survived to discharge (60/68, 88.2%). N-TPs who developed subacute groin complications had longer post-ECMO lengths of stay than those who did not (34 days, IQR 16-53 days vs. 17 days, IQR 8-34 days, P < 0.001). Post-ECMO length of stay was also longer among patients who underwent related surgical interventions compared to those who did not (50 days, IQR 35-67 days vs. 29 days, IQR 16-49 days, P = 0.007). Transplantation was the strongest risk factor for developing subacute groin complications (OR 3.91, CI95% 1.52-10.04, P = 0.005). Subacute groin complications and related surgical interventions are common after ECMO cannulation and are associated with longer hospital stays. When surgical management is warranted, muscle flaps may reduce lengths of stay compared to other surgical interventions.

First-in-man successful use of the SPECTRUM percutaneous dual-stage right ventricle and right atrium to pulmonary artery ventricular assist device.

BACKGROUND: Over the past decade, several minimally invasive mechanical support devices have been introduced into clinical practice to support the right ventricle (RV). Percutaneous cannulas are easy to insert, minimally invasive, and treat acute RV failure rapidly. In December 2021, the Food and Drug Administration approved a new 31 French dual lumen single cannula for use as a right ventricular assist device. AIMS: Descirbe the use of the new dual lumen percutaneous right ventricular assist device (RVAD) cannula. MATERIAL AND METHODS: Deployment of the RVAD can be done surgically or percutaneously. This cannula, manufactured by Spectrum, is dual staged. It has inflow ports positioned both in the right atrium (RA) as well as the RV for maximal drainage of the right heart. The distal end of the cannula which includes the outflow port is positioned in the pulmonary artery (PA). RESULTS: Deployment of the Spectrum RVAD can be done percutaneously with transesophageal and flouroscopy guidence. Cannulation requires requisite wire skills in order to navigate into the main pulmonary artery. Utilization of this cannula can be done in acute RV failure secondary to ischemia, post cardiotomy shock, acute respiratory failure or other causes of isolated RV failure. DISCUSSION: The dual stage drainage design optimizes venous drainage as well as limits suck-down events. Theoretically, direct RV decompression also decreases RV dilation and wall tension, and facilitates improved transmural pressure gradient to reduce RV strain. CONCLUSION: Here we describe the first-in-man successful use of the dual-stage RA and RV to PA Spectrum cannula in a patient with severe COVID acute respiratory distress syndrome and acute right ventricular failure, bridged to recovery.

How Should ECMO Be Used Under Conditions of Severe Scarcity? A Population Study of Public Perception.

OBJECTIVE: To assess societal preferences regarding allocation of extracorporeal membrane oxygenation (ECMO) as a rescue option for select patients with coronavirus disease 2019 (COVID-19). DESIGN: Cross-sectional survey of a nationally representative sample. SETTING: Amazon Mechanical Turk platform. PARTICIPANTS: In total, responses from 1,041 members of Amazon Mechanical Turk crowd-sourcing platform were included. Participants were 37.9 ± 12.6 years old, generally white (65%), and college-educated (66.1%). Many reported working in a healthcare setting (22.5%) and having a friend or family member who was admitted to the hospital (43.8%) or died from COVID-19 (29.9%). MEASUREMENTS AND MAIN RESULTS: Although most reported an unwillingness to stay on ECMO for >one week without signs of recovery, participants were highly supportive of ECMO utilization as a life-preserving technique on a policy level. The majority (96.7%) advocated for continued use of ECMO to treat COVID patients during periods of resource scarcity but would prioritize those with highest likelihood of recovery (50%) followed by those who were sickest regardless of survival chances (31.7%). Patients >40 years old were more likely to prefer distributing ECMO on a first-come first-served basis (21.5% v 13.3%, p < 0.05). CONCLUSION: Even though participants expressed hesitation regarding ECMO in personal circumstances, they were uniformly in support of using ECMO to treat COVID patients at a policy level for others who might need it, even in the setting of severe scarcity.

Increased Intracranial Hemorrhage Amid Elevated Inflammatory Markers in Those With COVID-19 Supported With Extracorporeal Membrane Oxygenation.

ABSTRACT: COVID-19-related coagulopathy is a known complication of SARS-CoV-2 infection and can lead to intracranial hemorrhage (ICH), one of the most feared complications of extracorporeal membrane oxygenation (ECMO). We sought to evaluate the incidence and etiology of ICH in patients with COVID-19 requiring ECMO. Patients at two academic medical centers with COVID-19 who required venovenous-ECMO support for acute respiratory distress syndrome (ARDS) were evaluated retrospectively. During the study period, 33 patients required ECMO support; 16 (48.5%) were discharged alive, 13 died (39.4%), and 4 (12.1%) had ongoing care. Eleven patients had ICH (33.3%). All ICH events occurred in patients who received intravenous anticoagulation. The ICH group had higher C-reactive protein (P = 0.04), procalcitonin levels (P = 0.02), and IL-6 levels (P = 0.05), lower blood pH before and after ECMO (P < 0.01), and higher activated partial thromboplastin times throughout the hospital stay (P < 0.0001). ICH-free survival was lower in COVID-19 patients than in patients on ECMO for ARDS caused by other viruses (49% vs. 79%, P = 0.02). In conclusion, patients with COVID-19 can be successfully bridged to recovery using ECMO but may suffer higher rates of ICH compared to those with other viral respiratory infections.

A Case Series of Devastating Intracranial Hemorrhage During Venovenous Extracorporeal Membrane Oxygenation for COVID-19.

OBJECTIVE: Anticoagulation may be a challenge in coronavirus disease 2019 (COVID-19) extracorporeal membrane oxygenation due to endothelial injury and dysregulation of coagulation, which may increase the risk of thrombotic and bleeding complications. This report was created to describe the authors' single institutional experience, with emphasis on the high rate of intracranial hemorrhage for the first 10 patients with COVID-19 placed on venovenous extracorporeal membrane oxygenation (VV ECMO). DESIGN: Case series, retrospective analysis. SETTING: Single institution. PARTICIPANTS: Ten patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patient characteristics, mortality, stroke rate, and length of stay data were collected in all patients. In addition, laboratory values of D-dimer and C-reactive protein and standard measurements of prothrombin and activated partial thromboplastin time were collected on all patients. Ten patients, each confirmed with COVID-19 via reverse transcription-polymerase chain reaction, were supported on VV ECMO for acute respiratory distress syndrome (ARDS) for a mean duration of 9.4 ± 7 days. Four of 10 patients had hemorrhagic strokes, 3 of which resulted in death. At 30 days after initiation of VV ECMO, a total of 7 survivors included 6 patients discharged from the hospital and 1 patient who remained in the intensive care unit. CONCLUSIONS: In this small study of 10 patients, intracranial hemorrhage was a common complication, resulting in a high rate of death. The authors urge caution in the anticoagulation management of VV ECMO for patients with severe ARDS and COVID-19 patients. Close monitoring of all hematologic parameters is recommended during ECMO support while awaiting larger, multicenter studies to examine the best practice.

Treatment With Impella Increases the Risk of De Novo Aortic Insufficiency Post Left Ventricular Assist Device Implant.

BACKGROUND: Impella (Abiomed Inc, Danvers, MA) is a temporary mechanical support device positioned across the aortic valve, and can be used to support patient before LVAD implantation. There are no data on the incidence of aortic insufficiency (AI) in patients supported with Impella as a bridge to durable LVAD implantation. We sought to assess the incidence of AI in patients with Impella support as a bridge to durable left ventricular assist device (LVAD) implantation. METHODS: We reviewed all patients undergoing primary LVAD implantation at the University of Pennsylvania from January 2015 onward, comparing those supported with Impella as temporary mechanical support with those supported by either venoarterial extracorporeal life support or an intra-aortic balloon pump. We reviewed transthoracic echocardiography preoperatively, as well as at 1 week, 1, 3, 6, 9, and 12 months after LVAD implantation. RESULTS: A total of 215 echocardiograms were analyzed in 41 patients. Eleven patients were supported with Impella before LVAD implant-6 patients with Impella alone (5 with Impella CP, 1 with Impella 5.0) and 5 with Impella in conjunction with venoarterial extracorporeal life support (2 with Impella 2.5, 2 with Impella CP, and 1 with Impella 5.0). After LVAD implant, mild or moderate AI developed in 82% of patients supported with Impella (9 of 11) compared with 43% of those without Impella (13 of 30) (P = .038). CONCLUSIONS: Patients supported by Impella as a bridge to durable LVAD have a higher risk of developing AI. Further studies are needed to assess this risk as the use of the Impella increases.

Preclinical performance of a pediatric mechanical circulatory support device: The PediaFlow ventricular assist device.

OBJECTIVES: The PediaFlow (HeartWare International, Inc, Framingham, Mass) is a miniature, implantable, rotodynamic, fully magnetically levitated, continuous-flow pediatric ventricular assist device. The fourth-generation PediaFlow was evaluated in vitro and in vivo to characterize performance and biocompatibility. METHODS: Supported by 2 National Heart, Lung, and Blood Institute contract initiatives to address the limited options available for pediatric patients with congenital or acquired cardiac disease, the PediaFlow was developed with the intent to provide chronic cardiac support for infants as small as 3 kg. The University of Pittsburgh-led Consortium evaluated fourth-generation PediaFlow prototypes both in vitro and within a preclinical ovine model (n = 11). The latter experiments led to multiple redesigns of the inflow cannula and outflow graft, resulting in the implantable design represented in the most recent implants (n = 2). RESULTS: With more than a decade of extensive computational and experimental efforts spanning 4 device iterations, the AA battery-sized fourth-generation PediaFlow has an operating range of 0.5 to 1.5 L/min with minimal hemolysis in vitro and excellent hemocompatibility (eg, minimal hemolysis and platelet activation) in vivo. The pump and finalized accompanying implantable components demonstrated preclinical hemodynamics suitable for the intended pediatric application for up to 60 days. CONCLUSIONS: Designated a Humanitarian Use Device for "mechanical circulatory support in neonates, infants, and toddlers weighing up to 20 kg as a bridge to transplant, a bridge to other therapeutic intervention such as surgery, or as a bridge to recovery" by the Food and Drug Administration, these initial results document the biocompatibility and potential of the fourth-generation PediaFlow design to provide chronic pediatric cardiac support.

Heart valve scaffold fabrication: Bioinspired control of macro-scale morphology, mechanics and micro-structure.

Valvular heart disease is currently treated with mechanical valves, which benefit from longevity, but are burdened by chronic anticoagulation therapy, or with bioprosthetic valves, which have reduced thromboembolic risk, but limited durability. Tissue engineered heart valves have been proposed to resolve these issues by implanting a scaffold that is replaced by endogenous growth, leaving autologous, functional leaflets that would putatively eliminate the need for anticoagulation and avoid calcification. Despite the diversity in fabrication strategies and encouraging results in large animal models, control over engineered valve structure-function remains at best partial. This study aimed to overcome these limitations by introducing double component deposition (DCD), an electrodeposition technique that employs multi-phase electrodes to dictate valve macro and microstructure and resultant function. Results in this report demonstrate the capacity of the DCD method to simultaneously control scaffold macro-scale morphology, mechanics and microstructure while producing fully assembled stent-less multi-leaflet valves composed of microscopic fibers. DCD engineered valve characterization included: leaflet thickness, biaxial properties, bending properties, and quantitative structural analysis of multi-photon and scanning electron micrographs. Quasi-static ex-vivo valve coaptation testing and dynamic organ level functional assessment in a pressure pulse duplicating device demonstrated appropriate acute valve functionality.

Red Blood Cell Mechanical Fragility Test for Clinical Research Applications.

Red blood cell (RBC) susceptibility to mechanically induced hemolysis, or RBC mechanical fragility (MF), is an important parameter in the characterization of erythrocyte membrane health. The rocker bead test (RBT) and associated calculated mechanical fragility index (MFI) is a simple method for the assessment of RBC MF. Requiring a minimum of 15.5 mL of blood and necessitating adjustment of hematocrit (Ht) to a "standard" value (40%), the current RBT is not suitable for use in most studies involving human subjects. To address these limitations, we propose a 6.5 mL reduced volume RBT and corresponding modified MFI (MMFI) that does not require prior Ht adjustment. This new method was assessed for i) correlation to the existing text, ii) to quantify the effect of Ht on MFI, and iii) validation by reexamining the protective effect of plasma proteins on RBC MF. The reduced volume RBT strongly correlated (r = 0.941) with the established large volume RBT at matched Hts, and an equation was developed to calculate MMFI: a numerical estimation (R2 = 0.923) of MFI if performed with the reduced volume RBT at "standard" (40%) Ht. An inversely proportional relationship was found between plasma protein concentration and RBC MF using the MMFI-reduced volume method, supporting previous literature findings. The new reduced volume RBT and modified MFI will allow for the measurement of RBC MF in clinical and preclinical studies involving humans or small animals.

A Reusable, Compliant, Small Volume Blood Reservoir for In Vitro Hemolysis Testing.

Bench-top in vitro hemolysis testing is a fundamental tool during the design and regulatory safety evaluation of blood-contacting medical devices. While multiple published experimental protocols exist, descriptions of the test loop reservoir remain ambiguous. A critical fixture within the circuit, there is no readily available blood reservoir that ensures thorough mixing and complete air evacuation: two major factors which can affect results. As part of the Food and Drug Administration (FDA) Critical Path Initiative, we developed a three-piece reservoir consisting of a 3D-printed base, a plastic clamp set, and a medical-grade blood bag. This simple, reusable, and cost-effective design was used successfully in the hemolysis assessment of FDA benchmark nozzles and prototype rotary blood pumps, and may be useful as an integral component to any in vitro blood circulation loop.

Ex Vivo Assessment of a Parabolic-Tip Inflow Cannula for Pediatric Continuous-Flow VADs.

To address the challenge of unloading the left ventricle during pediatric mechanical circulatory support using next-generation rotary blood pumps, a novel inflow cannula was developed. This unique inflow cannula for pediatric, continuous-flow, left ventricular assist devices (VADs) with a parabolic-shaped inlet entrance was evaluated alongside a bevel-tip and fenestrated-tip cannula via an ex vivo, isolated-heart experimental setup. Performance was characterized using two clinical scenarios of over-pumping and hypovolemia, created by varying pump speed and filling preload pressure, respectively, at ideal and off-axis cannula placement to assess ventricular unloading and positional sensitivity. Quantitative and qualitative assessments were performed on the resultant hemodynamics and intra-ventricular boroscopic images to classify conditions of nonsuction, partial, gradual or severe entrainment, and ventricular collapse. The parabolic-tip cannula was found to be significantly less sensitive to placement position (p < 0.001) than the bevel-tip cannula under all conditions, while not statistically different from the fenestrated cannula. Visual analysis of the parabolic-tip cannula showed complete resistance to entrainment, whereas the fenestrated-tip had partial entrainment in 90% and 87% of the over-pumping and hypovolemic studies, respectively. We conclude that future pediatric VAD designs may benefit from incorporating the parabolic-tip inflow cannula design to maximize unloading of the left ventricle in ideal and nonoptimal conditions.

Mechanical blood trauma in assisted circulation: sublethal RBC damage preceding hemolysis.

After many decades of improvements in mechanical circulatory assist devices (CADs), blood damage remains a serious problem during support contributing to variety of adverse events, and consequently affecting patient survival and quality of life. The mechanisms of cumulative cell damage in continuous-flow blood pumps are still not fully understood despite numerous in vitro, in vivo, and in silico studies of blood trauma. Previous investigations have almost exclusively focused on lethal blood damage, namely hemolysis, which is typically negligible during normal operation of current generation CADs. The measurement of plasma free hemoglobin (plfHb) concentration to characterize hemolysis is straightforward, however sublethal trauma is more difficult to detect and quantify since no simple direct test exists. Similarly, while multiple studies have focused on thrombosis within blood pumps and accessories, sublethal blood trauma and its sequelae have yet to be adequately documented or characterized. This review summarizes the current understanding of sublethal trauma to red blood cells (RBCs) produced by exposure of blood to flow parameters and conditions similar to those within CADs. It also suggests potential strategies to reduce and/or prevent RBC sublethal damage in a clinically-relevant context, and encourages new research into this relatively uncharted territory.

Multilaboratory study of flow-induced hemolysis using the FDA benchmark nozzle model.

Multilaboratory in vitro blood damage testing was performed on a simple nozzle model to determine how different flow parameters and blood properties affect device-induced hemolysis and to generate data for comparison with computational fluid dynamics-based predictions of blood damage as part of an FDA initiative for assessing medical device safety. Three independent laboratories evaluated hemolysis as a function of nozzle entrance geometry, flow rate, and blood properties. Bovine blood anticoagulated with acid citrate dextrose solution (2-80 h post-draw) was recirculated through nozzle-containing and paired nozzle-free control loops for 2 h. Controlled parameters included hematocrit (36 ± 1.5%), temperature (25 °C), blood volume, flow rate, and pressure. Three nozzle test conditions were evaluated (n = 26-36 trials each): (i) sudden contraction at the entrance with a blood flow rate of 5 L/min, (ii) gradual cone at the entrance with a 6-L/min blood flow rate, and (iii) sudden-contraction inlet at 6 L/min. The blood damage caused only by the nozzle model was calculated by subtracting the hemolysis generated by the paired control loop test. Despite high intralaboratory variability, significant differences among the three test conditions were observed, with the sharp nozzle entrance causing the most hemolysis. Modified index of hemolysis (MIHnozzle ) values were 0.292 ± 0.249, 0.021 ± 0.128, and 1.239 ± 0.667 for conditions i-iii, respectively. Porcine blood generated hemolysis results similar to those obtained with bovine blood. Although the interlaboratory hemolysis results are only applicable for the specific blood parameters and nozzle model used here, these empirical data may help to advance computational fluid dynamics models for predicting blood damage.